Two studies yield markedly similar results

Action Points

Note that these studies were published as abstracts and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

TORONTO -- Two commonly used probiotic products had no effect on the course of acute gastroenteritis in infants and toddlers, researchers reported here.

Separate randomized controlled trials, with some overlap in the researchers, showed that commercially available products were no better than placebo in the ability to prevent moderate to severe disease in the period after diagnosis, according to presentations at the Pediatric Academic Societies (PAS) annual meeting.

There was no positive signal in the PECARN Probiotic Trial regardless of how the investigators parsed the results, stated David Schnadower, MD, of Washington University School of Medicine in St. Louis.

"Please take a few minutes to notice how consistently negative this study was," Schnadower asked the PAS audience.

The multi-center PECARN study tested 5 days of Lactobacillus rhamnosus GG (LGG), at a twice-a-day dose of 1.0 x 1010 colony forming units, compared with a placebo in children ages 3-48 months.

The primary outcome was the incidence of moderate to severe disease after discharge from the emergency department, as measured by a Modified Vesikari Scale score at least nine. The Vesikari scale takes into account seven variables, including duration of diarrhea, duration of vomiting, and fever.

In the other multiple-center study, called PROGUT, Stephen Freedman, MD, of the University of Calgary in Alberta, Canada, tested a slightly different product -- Lactobacillus rhamnosus R0011 and Lactobacillus helveticus R0052, at a twice-daily dose of 4.0 x 109 CFU, in a 95 to 5 ratio, for 5 days.

Children, ages 3-48 months, with acute gastroenteritis were given the product twice a day; the endpoint was moderate to severe disease within 14 days of randomization to the probiotic or placebo.

But Freedman also reported there was little to choose between placebo and product.

The exception, he said, was in a tertiary endpoint -- the daily average number of episodes of vomiting -- which was slightly but significantly higher in those taking the probiotics. Freedman said the difference, however, was small and might not be clinically significant.

In both studies, safety did not differ between the groups.

The use of probiotics for acute gastroenteritis is growing, Schnadower said, and a major meta-analysis in 2015 suggested a benefit. But the studies included in the analysis were mostly small and there were methodological limitations, he said.

The practice is growing despite the lack of "high-quality evidence," he said, so his group enrolled 971 children with acute gastroenteritis to test the issue.

The bottom line was that 11.8% of the children getting the probiotics went on to have moderate to severe disease compared with 12.6% of those on placebo. The difference yielded a relative risk 0.96 (95% CI 0.68-1.35).

In Canada, Freedman reported a markedly similar outcome among 827 children -- an odds ratio 1.06 for moderate to severe disease (95% CI 0.77-1.46).

Based on these results, "clinicians and families should use caution," commented PAS session co-moderator Michelle Stevenson, MD, of the University of Louisville.

The studies are "well-designed, multi-center rigorous trials ... that provide good evidence" that the studied probiotics are ineffective, Stevenson said. But she noted that they apply to "two specific formulations of probiotics."

Indeed, Freedman was careful to point out at the end of his talk that the "results do not imply that they can be generalized to all other probiotics in all doses."

And Schnadower commented, "This is the beginning of the science. It's a fascinating field and it's going to evolve significantly over the next many years."

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